miRNA-mRNA Profiling Reveals Prognostic Impact of Expression in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) with mutation is a disease driving genetic alteration with good prognosis. Although it has been suggested that mutation induces chemosensitivity in leukemic cells, the underlying cause for the better survival of mutated patients is still not clear. Mutant AML has a unique microRNA and their target gene (mRNA) signature compared to wild-type . Dynamic regulation of miRNA-mRNA has been reported to influence the prognostic outcome. In the present study, in silico expression data of miRNA and mRNA in AML patients was retrieved from genome data commons, and differentially expressed miRNA and mRNA among mutated ( = 21) and wild-type ( = 162) cases were identified to establish a dynamic association at the molecular level. In vitro experiments using high-throughput RNA sequencing were performed on human AML cells carrying mutated and wild-type allele. The comparison of in vitro transcriptomics data with in silico miRNA-mRNA expression network data revealed downregulation of . On establishing miRNA-mRNA interactive pairs, it has been observed that hsa-mir-215-5p (logFC: 0.957;  = 0.0189) is involved in the downregulation of (logFC: -0.481;  = 0.0464) in mutated AML. We demonstrated that transient expression of mutation upregulates miR-215-5p, which results in downregulation of . We have also shown using a rescue experiment that neutralizing miR-215-5p reverses the effect of mutation on . Using the leukemic blasts from AML patients, we observed higher expression of miR-215-5p and lower expression of in mutated patients compared to wild-type cases. The overall survival of AML patients was significantly inferior in high expressers compared to low expressers (20.3% vs. 58.5%,  = 0.018). The data suggest that dynamic miR-215- regulation is potentially modulated by mutation, which might serve as an explanation for the better outcome in mutated AML.